A major complication associated with hemorrhagic, septic or traumatic shock is pulmonary insufficiency. Major contributing factors to this pulmonary lesion appear to be microembolization produced by platelet aggregates and an inflammatory response marked by release of leukocyte lysomonal enzymes in pulmonary tissue. It is likely that the increased pulmonary arterial pressure observed during endotoxic shock is due to platelet aggregation, since this increase in pressure does not occur in saline perfused lungs. In addition, prostaglandin E1, which inhibits platelet aggregation and leukocyte lusosomal enzyme release prevents the pulmonary effects of endotoxin. On the other hand, agents such as aspirin which inhibit endogenous prostaglandin synthesis are also effective in preventing pulmonary changes occurring secondary to shock inducing stimuli. Thus it would appear that prostaglandins may be a chemical mediator of the pulmonary changes during shock as well as being capable of preventing these changes. The proposed study is directed toward a better understanding of the pathophysiologic effects of endogenous prostaglandins (particularly those of the E series) on the lung during shock states. Particular emphasis will be placed on the investigation of the biochemical changes produced by these acidic lipids that might lead to platelet aggregation and leukocyte lysosamal enzymes release resulting in pulmonary damage. Of particular interest is the effect of these agents on platelet cyclic nucleotide changes that might mediate an increase in the cohesiveness of these cells promoting aggregation. In addition, the effects of different prostaglandins and inhibitors of prostaglandin synthesis on the progression of pulmonary changes during shock will be investigated. Finally, Glucocorticoids (e.g. Methylprednisolone) will be studied with respect to their actions on platelet aggregation with special emphasis being placed on the possible effects of these agents on platelet cyclic nucleotides which might mediate the beneficial effects of these agents in preventing microaggregation.